Case Presentation: A 34-year-old male presented with past medical history only significant for occupational exposure to non-ionizing radiation and recent dog bite approximately a week ago. He came in with a chief complaint of intermittent episodic non-exertional chest pain, dizziness, vertigo, and darkened urine. He states this has been ongoing and most recently also developed a headache. During the hospitalization, as he was being worked up for hemolytic anemia found on labs, the patient also developed dizziness and anterograde amnesia that self-resolved after 72 hours. Laboratory and clinical workup was revealing for hgb 9.8 g/dl, elevated troponins, WBC 5.1 K/ul, LDH 268 U/L, Haptoglobin < 10 mg/dl, ESR 77, CRP 6.4, negative direct and indirect Coombs testing, no evidence of schistocytes or other abnormalities on blood smear.Coronary CT revealing for possibly myocarditis. Initial CT head and lumbar puncture were non-revealing. Serological microbial analysis was unremarkable. CT-Angiography, CT head, and MRI revealed new onset strokes in an embolic pattern not previously seen. Eventually, due to clinical suspicion for paroxysmal nocturnal hemoglobinuria (PNH), Glycosylphosphatidylinostiol(GPI) CD55/59 testing was performed and returned with 3.7% partial and 15.14% complete deficiency of surface protein, consistent with diagnosis of paroxysmal nocturnal hemogloburia. Due to the rarity of PNH presenting as a stroke, the test was confirmed on repeat. Patient was started on Eliquis due to increase risk of thrombosis and is to be evaluated for outpatient evaluation to start on anti-c5 biologic such as ravulizumab after proper vaccination against streptococcal and meningococcal infections.
Discussion: PNH is an X-linked acquired genetic mutation of hematopoietic stem cells involved in the production of glycosylphosphatidylinositol (GPI) surface protein which connects CD55 and CD59 for cellular modulation of complement activation(1). When these proteins are not on the surface of red blood cells, this leads to paroxysmal stress-induced complement-mediated hemolysis. Symptoms include thrombosis, shortness of breath, and fatigue(1). Laboratory findings are characteristic of hemolytic anemia without findings of auto-antibodies. Diagnosis is confirmed with flow cytometry for GPI associated CD55 and 59. Treatment revolves around anti-complement biologic therapies to avoid hemolysis with the ultimate goal of preventing hemolysis and need for transfusion(1). Without treatment, life span is significantly shortened to approximately 1 to 2 decades after diagnosis and development of the disease(1). With treatment, life expectancy approaches that of the population. The most frequent cause of mortality and morbidity in those with PNH is due to their hypercoagulable state (1). This case corroborates with the typical findings seen in PNH[LH1] I, however myocarditis is not typically reported nor exact source cannot be elucidated from clinical and laboratory diagnosis. Other studies indicate the theoretical that severe anemia can lead to cardiac cellular dysfunction(2).
Conclusions: Hemolytic anemia can present with elusive multiorgan system involvement. A rare but serious cause of this is PNH, clinical suspicion should remain high if infectious and other autoimmune causes have been ruled out as this can significantly increase lifespan. This is important as those who typically present are in their third and fourth decade of life(1)
